UNIPROT:B0FTZ7 - FACTA Search

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Query: UNIPROT:B0FTZ7 (catenin)
18,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecular analysis of the cadherin-catenin complex elucidated the central role of beta-catenin in this adhesion complex, as it binds to the cytoplasmic domain of E-cadherin and to alpha-catenin. beta-Catenin may also function in signalling pathways, given its homology to the gene product of the Drosophila segment polarity gene armadillo, which is known to be involved in the wingless signalling cascade. To study the function of beta-catenin during mouse development, gene knock-out experiments were performed in embryonic stem cells and transgenic mice were generated. beta-Catenin null-mutant embryos formed blastocysts, implanted and developed into egg-cylinder-stage embryos. At day 7 post coitum, the development of the embryonic ectoderm was affected in mutant embryos. Cells detached from the ectodermal cell layer and were dispersed into the proamniotic cavity. No mesoderm formation was observed in mutant embryos. The development of extraembryonic structures appeared less dramatically or not at all affected. Our results demonstrate that, although beta-catenin is expressed rather ubiquitously, it is specifically required in the ectodermal cell layer.
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PMID:Lack of beta-catenin affects mouse development at gastrulation. 858 67

Various types of tumors show aberrant expression and overexpression of epidermal growth factor (EGF) receptor and the degree of receptor expression correlates with a malignant phenotype in many epithelial tumors. However, in vitro evidence supporting the advantageous role of receptor overexpression is deficient. In this study, we compared the effects of exogenous EGF on the cell colony morphology in monolayer and collagen gel culture between HSC-1 squamous carcinoma cells overexpressing EGF receptor and their revertant subline cells. These cells formed coherent cell colonies under routine culture conditions, but addition of EGF induced dissociation of cell colonies within 24 h in the parent HSC-1 cells, though not in the subline cells. Since the colony dissociation apparently involved loss of cell-cell adhesion, we also studied the effects of EGF on E-cadherin expression and its function. Cell aggregation assays showed that EGF reduced E-cadherin function dose-dependently in the parent cells, but not in the subline cells. However, immunoblotting analysis and ELISA showed the absence of downregulation or degradation of E-cadherin. Instead, EGF tyrosine phosphorylated cadherin/catenin complex components including beta-catenin and increased the detergent solubility of E-cadherin in the parent cells. These results suggest that EGF modified the functional association between E-cadherin and actin filament through tyrosine phosphorylation of the cadherin/catenin complex and thereby made the adhesion molecule incompetent. Our results indicate that the ligand activation of overexpressed EGF receptor impairs E-cadherin-mediated cell-cell adhesion and causes dissociation of the squamous carcinoma cell colonies, which facilitates tumor cell invasion in vivo. This might be relevant to the advantageous role of EGF receptor overexpression in malignant phenotype of epithelial tumor cells.
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PMID:Ligand activation of overexpressed epidermal growth factor receptor results in colony dissociation and disturbed E-cadherin function in HSC-1 human cutaneous squamous carcinoma cells. 863 95

We characterized the role of the E-cadherin adhesion system in the formation of epithelial tight junctions using the calcium switch model. In MDCK cells cultured in low (micromolar) calcium levels, the tight junctional protein Zonula Occludens-1 (ZO-1) is distributed intracellularly in granular clusters, the larger of which codistribute with E-cadherin. Two hours after activation of E-cadherin adhesion by transfer to normal (1.8 mM) calcium levels, ZO-1 dramatically redistributed to the cell surface, where it localized in regions rich in E-cadherin. Immunoprecipitation with ZO-1 antibodies of extracts from cells kept in low calcium and 2 h after shifting to 1.8 mM Ca2+ demonstrated the association of ZO-1 with alpha-, beta-, and gamma-catenins. E-cadherin was not detected in the ZO-1 immunoprecipitates but it was found in beta-catenin immunoprecipitates that excluded ZO-1, suggesting that the binding of ZO-1 to catenins may weaken the interaction of these proteins with E-cadherin. Immunofluorescence and immunoelectron microscopy confirmed a close association of beta-catenin and ZO-1 at 0 and 2 h after Ca2+ switch. 48 h after Ca2+ switch, upon complete polarization of the epithelium, most of the ZO-1 had segregated from lateral E-cadherin and formed a distinct, separate apical ring. The ZO-1-catenin complex was not detected in fully polarized monolayers. MDCK cells permanently transformed with Moloney sarcoma virus, which expresses low levels of E-cadherin, displayed clusters of cytoplasmic ZO-1 granules and very little of this protein at the cell surface. Upon transfection with E-cadherin into Moloney sarcoma virus-MDCK cells, ZO-1 redistributed to E-cadherin-rich lateral plasma membrane but later failed to segregate into mature tight junctions. Our experiments suggest that catenins participate in the mobilization of ZO-1 from the cytosol to the cell surface early in the development of tight junctions and that neoplastic transformation may block the formation of tight junctions, either by decreasing the levels of E-cadherin or by preventing a late event: the segregation of tight junction from the zonula adherens.
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PMID:Catenins and zonula occludens-1 form a complex during early stages in the assembly of tight junctions. 863 21

p120cas (CAS) is a protein tyrosine kinase substrate that associates directly with the cytoplasmic tail of the cell-cell adhesion molecule E-cadherin. CAS is thus part of a multimolecular complex that, along with other cadherin-binding proteins (catenins), mediates interactions between E-cadherin and the actin cytoskeleton. Down-regulation of E-cadherin expression and defects in catenin function have been implicated in tumor metastasis, but the role of CAS in these processes has not been addressed. Recently, the study of CAS was complicated when new anti-CAS antibodies revealed the presence of at least four putative CAS isoforms that appeared to vary in abundance between cell types. Here, we identify the four major isoforms expressed in murine fibroblasts, and we show that they are products of alternative splicing. Analysis of CAS isoforms in a variety of murine cell lines indicates that motile cells like fibroblasts and macrophages preferentially express CAS1 (i.e., CAS1A and CAS1B isoforms), and epithelial cells preferentially express CAS2 (i.e., CAS2A and CAS2B isoforms), whereas nonadherent cells (e.g., B cells, T cells, and myeloid cells) do not express detectable levels of CAS. Interestingly, CAS1 expression is dramatically up-regulated in a Src-transformed Madin-Darby canine kidney cell line, indicating that the pattern of isoform expression can be altered by cell transformation. Analysis of a variety of differentiated and metastatic human tumor cell lines reveals that CAS isoform expression in these cells is quite heterogeneous. Furthermore, several poorly differentiated cell lines fail to express particular isoforms that are typically observed in well-differentiated cell lines. These data raise the possibility that unbalanced expression of CAS isoforms in human carcinomas may influence cadherin function and contribute to malignant or metastatic cell phenotypes.
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PMID:Identification of murine p120 isoforms and heterogeneous expression of p120cas isoforms in human tumor cell lines. 865 9

Catenins (alpha, beta, and gamma) are a group of proteins linking E-cadherin with the cytoskeleton. Reduced expression of alpha catenin has been shown in some cancer lines and tissues and is related to the invasive nature of tumour cells. This study examined the effects of n-6 PUFAs on the expression of catenins in a range of human cancer cells by Western blotting. Although most of the cell lines expressed similar levels of beta and gamma catenins, a number of cell lines expressed low levels of alpha catenin. Treatment of cells with gamma linolenic acid (GLA) increased alpha catenin expression in most cell lines, while beta catenin levels were reduced, and gamma catenin expression was unchanged. Linoleic acid and arachidonic acid had not significant effects. We conclude that in human cancer cell lines, the expression of alpha and beta catenins can be regulated by gamma linolenic acid.
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PMID:Expression of catenins in human cancer cells and its regulation by n-6 polyunsaturated fatty acids. 866 25

Cadherins are homotypic adhesion molecules that classically mediate interactions between cells of the same type in solid tissues. In addition, E-cadherin is able to support homotypic adhesion of epidermal Langerhans cells to keratinocytes (Tang, A., Amagai, M., Granger, L. G., Stanley, J. R. & Udey, M. C. (1993) Nature (London) 361, 82-85) and heterotypic adhesion of mucosal epithelial cells to E-cadherin-negative intestinal intraepithelial T lymphocytes. Thus, we hypothesized that cadherins may play a wider role in cell-to-cell adhesion events involving T lymphocytes. We searched for a cadherin or cadherins in T lymphocytes with a pan-cadherin antiserum and antisera against alpha- or beta-catenin, molecules known to associate with the cytoplasmic domain of cadherins. The anti-beta-catenin antisera coimmunoprecipitated a radiolabeled species in T-lymphocyte lines that had a molecular mass of 129 kDa and was specifically immunoblotted with the pan-cadherin antiserum. Also, the pan-cadherin antiserum directly immunoprecipitated a 129-kDa radiolabeled species from an 125I surface-labeled Jurkat human T-cell leukemic cell line. After V8 protease digestion, the peptide map of this pan-cadherin-immunoprecipitated, 129-kDa species exactly matched that of the 129-kDa species coimmunoprecipitated with the beta-catenin antiserum. These results demonstrate that T lymphocytes express a catenin-associated protein that appears to be a member of the cadherin superfamily and may contribute to T cell-mediated immune surveillance.
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PMID:Expression of a candidate cadherin in T lymphocytes. 869 57

1. HT-29 M6 cells are a subpopulation of HT-29 cells that, contrarily to the parental cells, establish tight cell contacts and differentiate. Cell-to-cell contacts in HT-29 M6 cells are also regulated by protein kinase C; addition of the phorbol ester phorbol 12-myristate 13-acetate (PMA) decreases the homotypic contacts of these cells. We show here that HT-29 cells or HT-29 M6 cells treated with PMA contain lower levels of functional E-cadherin, determined by analysing the association of this protein with the cytoskeleton. No significant differences in the localization of alpha-, beta-, or p120-catenins were detected under the three different conditions. 2. Dysfunction of E-cadherin can be reversed by incubation of HT-29 cells with the tyrosine kinase inhibitor herbimycin A. On the other hand an augmentation of c-src activity in HT-29 cells or HT-29 M6 cells treated with PMA was observed with respect to control HT-29 M6 cells. The phosphorylation status of catenins was also investigated; in HT-29 or in HT-29 M6 cells treated with PMA, dysfunction of E-cadherin was accompanied by an increased phosphorylation of p120-catenin and by an elevated association of this protein to E-cadherin. These results suggest a role for pp60src and the pp60src substrate p120-catenin in the control of E-cadherin function in HT-29 cells.
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PMID:Intestinal HT-29 cells with dysfunction of E-cadherin show increased pp60src activity and tyrosine phosphorylation of p120-catenin. 869 75

DNA sequences encoding a novel member of the receptor protein tyrosine phosphatase (R-PTP) family, termed PCP-2, were identified in a human pancreatic adenocarcinoma cDNA library. Human PCP-2 cDNA predicts a protein of 1430 amino acids with a calculated Mr of 160 kDa. The predicted PCP-2 enzyme consists of a 740 amino acid extracellular region, a single transmembrane domain, and a 666 amino acid intracellular portion. The extracellular sequence contains a MAM (meprin/A5/PTPmu) domain, an immunoglobulin-like domain and four fibronectin type III-like repeats, suggesting that it is a member of the PTPkappa and PTPmu subfamily. The intracellular region contains two tandemly-repeated protein tyrosine phosphatase domains. Northern blot analyses revealed a single transcript of 5.5 kilobases, which is expressed at different levels in many human tissues except spleen and placenta. Upon transfection of PCP-2 cDNA into human embryonic kidney fibroblast 293 cells, a protein with an apparent Mr of 180 000 was detected by immunoblot analysis. This size was reduced to the predicted Mr upon treatment with endoglycosidase F, indicating that PCP-2 is glycosylated and, hence, expressed at the cell surface. A potential role of PCP-2 in cell-cell recognition and adhesion is supported by its co-localization with cell adhesion molecules, such as catenin and E-cadherin, at sites of cell-cell contact.
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PMID:Characterization of PCP-2, a novel receptor protein tyrosine phosphatase of the MAM domain family. 870 May 14

A number of genetic changes have been documented in prostate cancer, ranging from allelic loss to point mutations and changes in DNA methylation patterns. Up to now among the most consistent changes are those of allelic loss events, with the majority of tumours examined showing loss of alleles from at least one chromosomal arm. Chromosomes 8 and 13 appear to be the most frequently affected, with the former showing both loss of alleles from the short arm and gain of sequences on the long arm. Deletions of one copy of the RB gene are common, whereas deletion and/or point mutation of the TP53 gene is a less frequent event, at least in clinically localized tumours. Alterations in the E-cadherin/alpha catenin mediated cell-cell adhesion mechanism appear to be present in over one third of all prostate cancers and may be critical to the acquisition of metastatic potential of aggressive prostate cancers. In addition, altered DNA methylation patterns have been found in the majority of prostate cancers examined, suggesting an important role for methylation modulated gene expression in prostate carcinogenesis. Finally, the existence of prostate cancer susceptibility genes is suggested by study of familial clustering of prostate cancer, and it is expected that the identification of these genes will provide insight into critical rate limiting steps in the carcinogenic pathway of both inherited and sporadic disease.
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PMID:Molecular genetics of prostate cancer. 871 27

Desmosomes are intercellular adhesive junctions that associate with the intermediate filament cytoskeleton. The two major classes of transmembrane desmosomal glycoproteins, desmogleins and desmocollins, are widely considered to function as adhesion molecules. This assumption is based in part on their homology to the cadherin family of calcium-dependent homophilic adhesion molecules. In addition, autoantibodies from pemphigus patients bind directly to desmoglein family members and are thought to cause epidermal blistering by inhibiting the function of these cadherins. To directly test the ability of the desmosomal cadherins to mediate adhesion, desmoglein-1 (Dsg1), desmocollin-2 (Dsc2a) and plakoglobin were expressed in mouse L cell fibroblasts. Similar to catenin:classical cadherin complexes, plakoglobin:Dsc2a complexes exhibited an approximately 1:1 stoichiometry; however, plakoglobin:Dsg1 complexes exhibited a 6:1 stoichiometry. When L cells expressing the desmosomal cadherins were tested for the ability to aggregate in suspension, L cells expressing E-cadherin exhibited extensive aggregation, but L cells expressing Dsg1 or Dsc2a did not aggregate. In addition, L cells co-expressing Dsg1, Dsc2a, and plakoglobin failed to aggregate. The cytoplasmic domain of E-cadherin is thought to play a central role in the adhesive function of E-cadherin by providing a link to the actin cytoskeleton. Therefore, two chimeric cadherins comprising the cytoplasmic domain of E-cadherin and the extracellular domain of either Dsg1 or Dsc2a were expressed in L cells. Both chimeras formed a complex with alpha- and beta-catenin. Nevertheless, neither of these chimeras supported aggregation of L cells when expressed individually or when co-expressed. These data suggest that the extracellular domains of the desmosomal cadherins exhibit functional properties distinct from those of the classical cadherins, such as E-cadherin.
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PMID:Analysis of desmosomal cadherin-adhesive function and stoichiometry of desmosomal cadherin-plakoglobin complexes. 875 59

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